A three-page paper entitled “A case of glioma (embryonal neurocytoma) of the brain simulating pituitary tumour,” written by K. G. Pandalai, Surgeon at the Madras General Hospital, and T. B. Menon, Pathologist at the Madras Medical College, was published in the Indian Medical Gazette. This paper refers to an occasional finding of a brain tumor (a glioma), presurgically diagnosed as a pituitary tumor, in 1928. This was close to the period when surgeons across the developed world believed in that cancers were by no means common among the native people of India as it was in Europe. Leopold Rogers of the Bengal Medical Service, Calcutta, in 1925 refuted this belief indicating that malignant tumors were equally common in Bengal (India) and England. Nevertheless, this report by Pandalai and Menon strikes a unique chord since the tumor was subsequently determined as a glioma – an embryonal neurocytoma -– with adequate evidences drawn from the state-of-the-art volume “A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis” by Percival Bailey and Harvey Cushing published in Philadelphia in 1926. This Pandalai-–Menon report impresses as pioneering and trailblazing, on a brain tumor detected in 1928, given that earliest exclusive departments of neurosurgery were established in Christian Medical College, Vellore, and Madras Medical College, Madras, by Jacob Chandy and Balasubramanian Ramamurthi, respectively, nearly two decades later.

William Jackson Elmslie (1832–1872), a Scottish missionary and a medical doctor attached to the Punjab Medical Mission Society, impresses as the earliest Western-medical practitioner, who formally recorded cancer in India. Elmslie's paper [1] relates to screening a little more than 5,000 Kashmiris, of whom he diagnosed epithelioma in 30, which he clinches as due to the kangris (the small clay pots containing hot embers customarily tied near stomachs beneath the massive traditional overalls) used by them to keep warm. Occasional reports on cancer incidence have since appeared in professional journals.[2] Recognition of cancer gained prominence in India in 1900–1910. Key examples would be the trend-setting papers by Surgeon William Niblock of the Madras General Hospital, who related oral cancers and tobacco chewing [3] and surgeon Ernest Neve attached to the Kashmir Mission Hospital, Srinagar, who dealt with the surgeries of different cancers along with his older brother Andrew Neve, another surgeon attached to the same hospital.[4] Publications of Niblock and Neve are milestones in the epidemiology of cancer in India, especially because a strong belief prevailed among many of the medical personnel of developed nations and those in India that cancers were rare in dark-skinned human races.[5] Robert A. Smith (American Cancer Society, Atlanta) in his “A brief history of cancer in India” (https://www.slideshare.net/RobertSmith691/history-of-cancer-in-india-report-71309201, accessed November 22, 2018) quotes the words of Walter James Buchanan (the editor of the Indian Medical Gazette [IMG], Calcutta, 1889–1919) dated 1900: “I do not think cancer or other malignant disease is by any means so common among natives in India as in Europe.” This belief was proved incorrect and fallacious in the immediately following decades.[6] Leopold Rogers of the Bengal Medical Service [7] in the Finlayson lectures delivered in Glasgow categorically said that malignant tumors, including both connective-tissue and epithelial types, were equally common in Bengal and England. Rogers made this statement by comparing 1,067 postmortem examinations done in Calcutta Medical College with c. 1,000 postmortem examinations done in St. Mary's Hospital, London. This point has been reinforced in the later decades of the 20th century by the Indian pathologist Vasant Ramji Khanolkar [8] and the Scottish oncologist Malcolm Stewart Muir,[9] who spent most of his work time in Singapore.

In such a messy context of epidemiology of cancers in the early decades of the 20th century, brief biographical details and a photograph of K. G. Pandalai are available in the Association of Surgeons of India website and in his obituary.[10],[11] Similar details of T. B. Menon are available in I. B. Rao.[12],[13] Gopinath Pandalai, a surgeon of Madras, has etched his name in the chronicles of Madras' medical history by performing the first successful gastrectomy to treat duodenal ulcer in the Madras General Hospital in 1926.[14] Nonetheless, the Pandalai–Menon article deals with the diagnosis and surgery of a distinct type of a brain tumor at the Madras General Hospital. Since very little of the subtle variants of brain tumors was known in India in the 1920s, this article highlights some of the fascinating dimensions of what was initially diagnosed as a pituitary tumor by Pandalai, but later determined as a glioma (an embryonal neurocytoma) of the brain by Menon.

Pandalai-–Menon case report in Indian Medical Gazette (1928)

This report pertains to a 30-year-old Indian male, identified as “T.V.” admitted into the surgical ward of Madras General Hospital on January 22, 1928. T.V. had a history of 6-month-long severe headache, gradually increasing dimness of vision, and double exophthalmos with occasional vomiting. Sharply recorded case notes are available: bilateral exophthalmos more marked in the right eye, marked papilledema on both sides with left-sided facial paralysis, Romberg's sign present, X-ray film revealed enlarged pituitary fossa and the shadow of a tumor with a calcified center, and the Wassermann reaction was negative.

The primary diagnosis was that a tumor occurred in front of the chiasma, pressing on the optic nerve on both sides causing either widening or erosion of sella turcica, impeding the venous circulation on both sides inducing exophthalmos. Although symptoms of endocrine disturbance were not apparent, a tumor causing such bilateral signs was a high possibility, one of pituitary origin.

Surgery was carried out on February 1, 1928, using rectal-ether anesthesia along with locally administered procaine. The surgical procedure included the following steps: A large (dimensions not supplied) frontoparietal osteoplastic flap was raised. The dura was opened but the brain bulged out by an inch (2.54 cm). While attempting to lift the frontal lobe, the pressure was high and the cortex tore. Therefore, Pandalai decided to repeat the procedure a few days later. The bone flaps were removed enabling skin suturing. Unfortunately, the patient died on February 7, 1928, without gaining consciousness.

Bhaskara Menon supplies pathological notes. The tumor had arisen from the floor of the third ventricle connected with the optic thalami. It had grown forward underneath the frontal lobes as a soft, grey mass of the size of an orange (dimensions not supplied; possibly 4-5 cm wide). The tumor had made its way downward displacing the frontal lobes. It was hanging as a pedunculated mass. It had perforated the ethmoid plates on both sides. Through the ethmoid bone, it had made its way into the orbit causing diffuse infiltration of the tissues of both eyes, building pressure on optic nerves, and thus causing bilateral exophthalmos. The tissue was soft, friable with minute haemorrhages. The neoplastic tissue on the left side was hard to distinguish from the normal brain tissue, where it had infiltrated the pia mater and the dura mater at the base of the brain. But the tissue mass on the right side was well defined, and therefore, the point of origin could be determined.

Histological examination of the tumor included either rounded or cuboidal cells occasionally dispersed with fibrils. The fibrils presented a palisade arrangement. No pseudo-rosettes were evident, but in certain areas, clusters of fibrils around blood vessels were apparent. These details prompted that this could have been a round-celled sarcoma.

Pandalai and Menon discuss their findings using the then state-of-the-art book on the classification of tumors of the glioma group by Percival Bailey and Harvey Cushing.[15] Based on the Bailey-–Cushing classification, Pandalai and Menon subsequently determine this tumor as an embryonal neurocytoma (a glioma), since this tumor grew out of the embryonal cells lining the medullary plate. The fibrils had grown from the neurocytes, which Pandalai and Menon identified as spongioblasts. They reported a supplementary comment that neurocytomas of similar structure can originate in the retinae of children and can spread into the brain and sometimes onto the other eye.

» Remarks

Pandalai's preliminary diagnosis as a pituitary tumour (an adenoma?)

In p. 580, Pandalai says,

“The diagnosis was a tumour in the region in front of the chiasma pressing on the optic nerves on both sides, causing widening or erosion of the sella turcica and impeding the venous circulation on both sides resulting in exophthalmos. Though signs of endocrine disturbance were not noticeable, a tumour which could cause such bilateral signs was regarded as possibly of pituitary origin.”

The present understanding of pituitary tumors is that they develop from pituitary gland and not from brain tissues. A majority of them are benign. Because they arise from an endocrine organ of the body, the tumors can induce them to produce hormones excessively, resulting in fatigue, menstrual irregularities, and either weight gain or weight loss, besides many other undesirable effects. Most pituitary tumors are common among 30- to 50-year-old people. When they become large, they can compress optic nerves resulting in vision disturbances (https://www.cancercenter.com/brain-cancer/types/tab/other-brain-tumors/accessed on November 22, 2018). In a such modern-day understanding of pituitary tumors, the preliminary diagnosis by Pandalai, given that the year was 1928, on examining the patient, strikes as impressive, considering the differentials he used at this point.

In 1884–1886, histological characterization was used first to understand and recognize cell physiology in pituitary tumors.[16] Such a practice led to linking abnormal cytological features with clinical features. In 1900, Carl Benda [17] showed that adenomatous cells stained positively with eosin. This finding paved the way of using histological techniques in studying tumors and to correlate histological features with clinical presentations. Histopathological determinations necessarily require tissue sampling via surgical procedures. From 1909, Harvey Cushing in Baltimore approached the pituitary, taking a sublabial-submucosal-transseptal path. However, craniotomy replaced this in 1927. Bailey and Cushing [15] showed the striking relationships between macromorphological features of the tumors and histological presentations of glial tumors. They illustrated that the cells of astrocytomas appear similar to astrocytes; so much so those of oligodendrogliomas resemble oligodendrocytes. As these tumors grew further, their cells resembled the less-differentiated precursor cells, the astroblastomas. Although these propositions were trailblazing and constructed in the second half of the 20th century, many finer details are still unclear.[18]

Surgical intervention by Pandalai

Even in the developed world, single-modality approach was preferentially used to treat gliomas until the 1950s. Surgery was the procedure of choice in “treating” various types of cancers historically.[19] The logic was the excision of malignant growth as completely and as quickly as possible would relieve the metabolic interference with normal functions by the abnormal growth and obviate the possibility of metastatic spread. This -– customarily referred as the classical approach was developed by William Halsted in 1894.[20] Halsted believed that the principal danger of cancer dissemination occurred by direct movement of malignancy from the original lesion to surrounding tissues. Although this is currently challenged,[21] this is being followed by surgeons, dictated by circumstances. Today, the treatment and management of various types of gliomas are done recruiting multidisciplinary teams, because a strategic combination of diverse-treatment methods helps improve disease prognosis and reduce recurrence. Multimodality-glioma-therapy has evolved in such a manner that it is tailored to suit individual patients depending on tumor grade and histological and molecular subtypes.[22]

Pandalai uses the term “rectal-ether anesthesia” during the preparation of the patient for surgery. Rectal-ether anesthesia refers to the instillation of an anesthetic solution (usually a central-nervous-system depressant) via rectum. The strengths and weaknesses of this practice and the methods of application of rectal-ether anesthesia are available in Hatcher.[23] This method of anesthetics in surgical practice was proposed by Marc Dupuy in Paris in a brief note entitled Note sur les effets de l'injection de l'éther dans le rectum sent to l'Académie des Sciences, Paris (l'ASP), in March 1847.[24] Nikolai Pirogoff in Moscow submitted a note Nouveau procédé pour produir, au moyen de la vapour d'éther, l'insensibilité chez les individus soumis a des opérations chirurgicals to l'ASP, independent of Dupuy, in May 1847.[25] James Gwathmey, an American surgeon recognized for his work in anesthesiology, was one of the strong advocates of rectal administration of ether oil. Joseph Blomfield, a British surgeon, recommended that the rectal route was useful “in certain circumstances.” Edgar Stanley Rowbotham, another British surgeon and a strong propagandist of local anesthesia, always spoke of rectal routes for anesthetics was a considerate way, especially while treating children. The discovery of avertin (bromethol) in 1929 led to its increased use in general surgical and obstetrical procedures, along with rectal route of ether administration.[26]

The tumour was determined as a glioma (an embryonal neurocytoma) by Bhaskara Menon

In pp. 580-581, Menon says,

“Following Bailey and Cushing's division of the gliomata into thirteen different groups, one would place this tumour among the embryonal neurocytomata, which are tumours derived from the embryonal cells that line the medullary plate. With regard to the origin of these fibrils one view is that the neurocytes themselves form fibres in the process of development into what have been called spongioblasts. Another view is that the fibrils are derived from neuroglia cells which are included in the growth. Whatever view is correct, it must be understood that the neurocyte is the cell that forms the medullary epithelium of the medullary groove which forms the brain vesicles. Some of these cells become elongated and form fibres and are called spongioblasts which are the precursors of the adult neuroglia cells, the astrocytes. Others become differentiated into neuroblasts which are the precursors of the nerve cells. It is of interest to note that neurocytomas of similar structure may originate in the retina in children and spread up into the brain and even to the corresponding eye.”

Bailey and Cushing [15] indicate that gliomas are primary tumors, which have significantly different biological properties, prognoses, and treatment approaches. Today we recognize by gliomas based not only on their histopathology but also applying molecular parameters.[27],[28] Their comment on the similarity between retinoblastoma and glioma is striking, since, a little before this procedure done at Madras General Hospital, Frederick Verhoeff and Edward Jackson [29] had published their work on retinoblastomas.

Less-important points

Certain technical terms which Pandalai and Menon used in their article are not acknowledged to their original sources. For example, “spongioblasts” and “neurocytes” are from Keibel and Mall [30] available in p. 5 and p. 147, respectively. The term “neurocytoma” was first used by Wright.[31] “Neurocytomata” is the accepted plural form for “neurocytoma” further to “neurocytomas” (https://www.merriam-webster.com/medical/neurocytoma, accessed November 22, 2018).

» Conclusion

Although brief, the note by Pandalai and Menon establishes itself as a ground-breaking report on a brain tumor detected in Madras in 1928. The chapter History of Neurosurgery[32] does not speak of any similar surgery done in preindependent India. We, therefore, see this as a trailblazing report, given that exclusive departments of neurosurgery were established in the Christian Medical College and Hospital, Vellore, and Madras General Hospital, Madras, by Jacob Chandy and Balasubramaniam Ramamurthi, respectively, 21 years later!

» Acknowledgements

We are grateful to David Dance (Lao–Oxford–Mahosot Hospital–Wellcome Trust Research Unit, Nuffield Medical Sciences Division, University of Oxford, Oxford, UK) for help. Thanks are also due to the editor of IMG for permitting us to use the Pandalai-Menon paper published in IMG (1928) (vide email from Partha Roy, dated November 29, 2018).